Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.
School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, New South Wales, Australia.
Nat Med. 2024 Jul;30(7):1913-1922. doi: 10.1038/s41591-024-03044-0. Epub 2024 Jun 6.
Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment (PGT). Here we report consecutive data from 384 patients with high-risk pediatric cancer (with an expected cure rate of less than 30%) who had at least 18 months of follow-up on the ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial. A total of 256 (67%) patients received PGT recommendations and 110 (29%) received a recommended treatment. PGT resulted in a 36% objective response rate and improved 2-year progression-free survival compared with standard of care (26% versus 12%; P = 0.049) or targeted agents not guided by molecular findings (26% versus 5.2%; P = 0.003). PGT based on tier 1 evidence, PGT targeting fusions or commenced before disease progression had the greatest clinical benefit. Our data show that PGT informed by comprehensive molecular profiling significantly improves outcomes for children with high-risk cancers. ClinicalTrials.gov registration: NCT03336931.
最近的研究表明，精准医学可以为儿童癌症患者确定新的治疗策略。然而，目前尚不清楚哪些患者将从精准指导治疗（PGT）中获益最大。在这里，我们报告了连续 384 名患有高危儿科癌症（预期治愈率低于 30%）患者的随访时间至少为 18 个月的结果，这些患者均参加了 ZERO 儿童癌症精准医学计划 PRISM 试验。共有 256 名（67%）患者接受了 PGT 推荐，110 名（29%）患者接受了推荐的治疗。PGT 导致客观缓解率提高了 36%，与标准治疗（26%比 12%；P=0.049）或未根据分子发现指导的靶向药物治疗（26%比 5.2%；P=0.003）相比，2 年无进展生存率得到了改善。基于 1 级证据的 PGT、针对融合的 PGT 或在疾病进展前开始的 PGT 具有最大的临床获益。我们的数据表明，基于全面分子分析的 PGT 显著改善了高危癌症患儿的预后。临床试验注册：NCT03336931。
